Strategies for Revascularization in Patients Undergoing Heart Valve Surgery With Concomitant Coronary Artery Disease (SAVE-IT)

Strategies for Revascularization in Patients Undergoing Heart Valve Surgery With Concomitant Coronary Artery Disease. AngIography vs Fractional Flow Reserve

The purpose of this study is to determine whether, in patients undergoing elective valvular heart surgery, revascularization of concomitant coronary artery disease (CAD) guided by FFR (Fractional flow reserve) would be superior to standard angiography-guided-revascularization approach on major efficacy and safety outcomes

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Valvular Heart Disease
• Intervention / Treatment: Procedure: FFR-guided surgical revascularization; Procedure: Angio-guided surgical revascularization

Detailed Description

The SAVE-IT trial is a multicenter, international, randomized, controlled, superiority trial. Patients scheduled to undergo elective valvular heart surgery will be screened for presence of concomitant coronary artery disease (CAD) by invasive coronary angiography. Patients with a stenosis > 50% in at least one epicardial vessel (excluding left main) considered suitable for surgical revascularization will be randomized to FFR guided- or standard angiography-guided surgical revascularization. A proportion of patients with no concomitant CAD will be followed in a parallel registry

Baseline clinical, laboratory, electrocardiographic and echocardiographic data will be obtained. Coronary anatomy severity will be assessed by quantitative coronary angiography (QCA) and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (Syntax) score. Surgical risk will be assessed by Euroscore. Patients randomized to FFR-guided arm will have functional severity of the angiographic stenosis assessed by a St. Jude Medical coronary pressure wire measurement under hyperemic conditions using intravenous or intracoronary adenosine administration. If the FFR is ≤0.8 then a graft will be placed distal to the coronary stenosis. If the FFR is >0.8 no grafting will be performed to the epicardial vessel containing the stenosis. Patients will receive cardiac surgery no later than 8 weeks after randomization.

Peri-operative data will be collected. Clinical follow-up data will be collected at 1, 6 and 12 month after surgery. Graft patency at 12 months will be assessed by cardiac computed angiography (CCTA) for all patients who received at least one graft, except if an invasive coronary angiography has been performed in the preceding 3 months based on clinical grounds.

• Study Type: Interventional
• Enrollment (Anticipated): 502
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruben Ramos, MD; Phone Number: +351963156910; Email: ruben.a.b.ramos@gmail.com
• Study Contact Backup: Name: Mafalda Selas, RN; Phone Number: +351213594000

Study Locations

• Portugal
  • Lisbon, Portugal, 1169-024
    • Recruiting
    • Hospital Santa Marta, centro Hospitalar Lisboa Central
    • Contact: Ruben Ramos, MD; Phone Number: +351963156910; Email: ruben.a.b.ramos@gmail.com
    • Contact: Mafalda Selas, RN; Phone Number: +351213594000; Email: mafalda.selas@gmail.com
    • Principal Investigator: Ruben Ramos, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Severe heart valve disease with indication for an elective cardiac with a St. Jude Medical Heart Valve
• Concomitant significant CAD (at least one epicardial vessel with a stenosis> 50%)
• Willing and able to provide informed written consent

Exclusion Criteria:

• Previous CABG
• Angiographic significant lesion involving left main lesion (patient is still eligible if right coronary artery is candidate for FFR measurement and surgical revascularization)
• All lesions in extremely tortuous or calcified coronary vessels
• Recent myocardial infarction (< 30 days)
• Cardiogenic shock or clinical instability (i.e. NYHA 4, uncontrolled arrhythmias, unexplained hypotension severe bradycardia or any other medical condition considered as a sign of instability by the assisting physician)
• Severe left ventricular dysfunction (EF < 35%)
• Pregnant or are planning to become pregnant during the duration of the investigation
• Chronic renal dysfunction as defined as estimated glomerular filtration rate < 60 ml/min
• Life expectancy < 12 months
• Currently participating in any other clinical investigation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FFR-guided revascularization; Patients with valvular heart disease scheduled for elective cardiac surgery and concomitant significant coronary artery disease will have FFR measured with a St. Jude Medical coronary pressure wire across all lesions in vessels pre-specified as suitable for surgical revascularization. If the FFR is ≤0.80, then CABG will be performed. If the FFR is >0.80 then no graft will be placed in that particular vessel. Patients in whom FFR of a particular lesion is not possible can be included if at least one additional lesion is suitable for FFR measurement and grafting.	Procedure: FFR-guided surgical revascularization; Other Names: Fractional Flow Reserve-Guided surgical revascularization
Active Comparator: Angio-guided revascularization; Concomitant CABG will be performed as per clinical routine in all vessels with at least one stenosis > 50%. The vessel should be pre-specified as suitable for surgical revascularization before randomization. An internal mammary graft to the LAD should be attempted in all cases, if possible. Further revascularization strategy is left to the discretion of each center.	Procedure: Angio-guided surgical revascularization; Other Names: Coronary artery bypass graft guided by angiographic-only assessment of severity stenosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCE	Composite endpoint of death, nonfatal myocardial infarction, unplanned revascularization and stroke at 12 months. Subjects who die or are lost to follow up before 1 year will be censored at their last recorded activity.	12 months
Graft failure	Graft patency as assessed by CCTA scheduled at 12 months. Graft status can also be assessed by invasive coronary angiography if clinically indicated.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCE	death, nonfatal myocardial infarction, unplanned revascularization and stroke	1 month
MACCE	death, nonfatal myocardial infarction, unplanned revascularization and stroke	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative atrial fibrillation rate	Occurrence of any documented episode of symptomatic or asymptomatic episode of atrial fibrillation	Participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Post operative ICU stay	From cardiac surgery end to transfer to intermediate care unit or ward. Measured in hours.	participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Hospitalization period	From cardiac surgery to hospital discharge. Measured in days.From date of cardiac surgery until the date of first hospital discharge assessed up to 8 weeks	expected average of ten days
Total circulatory bypass time	measured in minutes	expected maximum of 300 minutes
Total cross-clamp time	measured in minutes	expected maximum of 300 minutes
Acute renal injury	Percentage decline in glomerular filtration rate at post-operative day 4 as compared to pre-operative glomerular filtration rate	to post-operative day 4
Blood transfusion	Number of units of red blood cells transfused.	participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Duration of mechanical ventilation	Total duration of mechanical ventilatory support. Repeated intubation will be included	participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Time to inotropic weaning	Total time spent with inotropic support. Recurrent use will be quantified	participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Use of intra-aortic balloon pump (IABP)	Number of patients requiring mechanical hemodynamic support with IABP	participants will be followed for the duration of hospital stay, an expected maximum of 4 weeks
Anginal status	Symptomatic status as defined canadian cardiac society (CCS) anginal status score	12 months
Heart failure symptoms	Symptomatic status as defined per New York Heart Association (NYHA) score	12 months

Collaborators and Investigators

• Sponsor: Portuguese Society of Cardiology
• Collaborators: Abbott Medical Devices
• Investigators: Principal Investigator: Ruben Ramos, MD, Hospital Santa Marta, centro Hospitalar Lisboa Central; Principal Investigator: Sergio Batista, MD, Hospital Fernando da Fonseca; Principal Investigator: Luis Raposo, MD, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Central; Principal Investigator: Emanuele Barbato, PhD, Olzv-Aalst Clinic; Principal Investigator: Colin Berry, PhD, Golden Jubilee National Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: June 23, 2014
• First Posted (Estimate): June 25, 2014

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 20, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Coronary artery disease; Fractional flow reserve; Valvular heart disease; Coronary artery bypass surgery; Coronary graft failure or patency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Valve Diseases
• Other Study ID Numbers: SAVEIT351